Atrial fibrillation is a disease not necessarily confined to the atria, but rather a systemic disease. In the elderly patient, it is more commonly associated with aortic atherosclerosis, increased vascular stiffness, heart failure, diabetes hypertension, and age, although atrial anatomical remodeling, fibrosis, and endothelial dysfunction may be a final common pathway in many with this condition. It is therefore not surprising that among elderly patients with aortic valve disease—a process postulated to be driven by the same risk factors—this is associated with this rhythm disturbance. The paper by Tarantini et al. (1) in this issue of JACC: Cardiovascular Interventions draws the appropriate and rather unambiguous conclusions that the presence at baseline or subsequent development of atrial fibrillation negatively impacts most major clinical outcomes in patients undergoing transcatheter aortic valve replacement (TAVR).

It is well known that atrial fibrillation is associated with coronary bypass grafting, aortic valve replacement, other valve surgery, or even noncardiac surgery. So what new insights can we learn from the data provided by Tarantini et al. (1)? Why is this important? Or rather what implications does it have for the management of patients with aortic valve disease in which TAVR is contemplated?

The first question is whether this information influences the decision to consider the procedure? Typically these patients are highly symptomatic and not candidates for open valve surgery; and as such, the presence of atrial fibrillation has little impact on patient selection. It nevertheless should be seen as a risk factor for higher morbidity and mortality including stroke, and this aspect should be a critical part of informed decision making in discussions with the patient and his or her families.

Should the procedure itself be changed in any way based on this data? Although this is not new information (2) this study does provide significant substantiation that nontransfemoral approaches are associated with higher rates of atrial fibrillation. Most commonly dictated by anatomical constraints such as more advanced vascular disease, the nontransfemoral route appears to be associated with a higher likelihood of pre-existing atrial fibrillation and worse clinical outcomes at 30 days and 1 year (3), suggesting that this group may inherently have worse overall substrate. Interestingly, there has been no demonstration of higher stroke rates in the nontransfemoral patient group (4,5), yet both these fundamental elements require further validation.

Should these data change what we do perioperatively? Amiodarone (6), corticosteroids (7), and colchicine (8) have all been shown to reduce postoperative atrial fibrillation in patients undergoing cardiac surgery—yet no consistent benefit as far as stroke or mortality has been realized. It may therefore be premature to recommend these prophylactic strategies, and certainly this presents multiple opportunities for investigation to clarify whether potential value exists in preemptive antiarrhythmic or anti-inflammatory interventions in this high-risk population.

Probably the most important question clinicians should be asking in lieu of this data is whether the development of atrial fibrillation is a surrogate for a “sicker” group of patients, and does it identify a group of patients with a more complicated perioperative course. The data from this investigation does firmly support this with higher Society of Thoracic Surgeons (STS) scores at baseline, and higher rates of transapical access, larger prosthetic valves, general anesthesia, pre- or post-dilation and technical success. Were there more unrecognized thromboembolic downstream consequences? Was there a more dramatic change in their hemodynamics? Most of the questions remain unanswered, yet if this is an intrinsically sicker group of patients, are they not more likely to be at higher risk of all important clinical events following TAVR or any other invasive procedure? We do know from this dataset, that this group of elderly patients (average age of patients in this cohort is around 82 years) presenting with atrial fibrillation were more likely to have an implanatable cardioverter-defibrillator, a diagnosis of congestive heart failure, or diabetes. In addition, they were also more likely to have worse renal function—a higher incidence of chronic kidney disease—as well as more severe mitral regurgitation or pulmonary hypertension. And as final confirmation that this group of patients with atrial fibrillation is sicker—they have higher STS scores. This is the perennial dilemma of outcomes observed from observational studies and although multivariate analyses can adjust for baseline variables, they cannot eliminate them and confounders remain a fact of life. So whether atrial fibrillation is cause or consequence or surrogate, this certainly has a major impact on algorithms to prevent as opposed to simply managing this outcome.

Important data on utilization of anticoagulants is somewhat surprisingly not provided by the anticoagulation status in this study (1), but the results suggest that there was no increase in thromboembolic events and is likely confounded by the differential use of anticoagulation—and gets to a crucial question regarding the timing of anticoagulation. It is fundamental to realize that if these patients develop atrial fibrillation, then almost always anticoagulation should be prescribed (as typically the TAVR patient will also have an elevated CHA2DS2-VASc score). These data (as well as other registry studies) (2) highlights that stroke is more common at the 2-year follow-up—but only in those patients who developed atrial fibrillation after the procedure. These provocative findings suggest that atrial fibrillation potentially recurs, and that perhaps the anticoagulation had been discontinued. This postulate requires confirmation, yet is analogous in some ways to the rhythm-control arm of the large AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial (9) in that many of the strokes occurred in patients who reverted back to sinus rhythm but presumably continued to sustain untreated AF recurrences (in the context of no anticoagulation). It is always difficult to know how long to continue anticoagulation in the context of atrial fibrillation that develops perioperatively, but we do see this as evidence that atrial fibrillation likely recurs and these patients have a universally higher risk of stroke (based on the CHA2DS2-VASc score). Strong consideration should therefore be given to long-term anticoagulation yet weighed against the risk of bleeding. This is emphasized by the results of this analysis reflecting that bleeding (and even major bleeding) is more common in these patients with atrial fibrillation. This higher rate of bleeding was also seen in patients enrolled in the PARTNER (Placement of Aortic Transcatheter Valve) trial, and therefore begs the question whether direct oral anticoagulants should be utilized in preference of warfarin—given their superior bleeding profiles. Unfortunately, not even the GALILEO (Global Study Comparing a rivAroxaban-based Antithrombotic Strategy to an antipLatelet-based Strategy After Transcatheter aortIc vaLve rEplacement to Optimize Clinical Outcomes) trial (comparing a rivaroxaban-based anticoagulation strategy, following successful TAVR, with an antiplatelet-based strategy) will address the optimal duration of therapy, as the Xa inhibitor is prescribed for only the first 90 days. Emerging wireless technologies for longer term monitoring are also likely to play an important role in identifying patients with subclinical atrial fibrillation; but also as powerful diagnostic tools for investigation to better define the cohort at highest risk.

In summary, it is clear that those patients with pre-existing atrial fibrillation and those who develop atrial fibrillation at the time of TAVR are sicker patients with higher STS scores. There is now consistent evidence that nontransfemoral approaches are associated with provocation of new-onset atrial fibrillation—and it is critical for clinicians to realize that if this occurs, anticoagulation should likely be continued longer term to avoid the occurrence of late stroke. This study raises some provocative questions for which we do not have evidence-based answers but it would be a ripe subject for prospective trials.

Footnotes

↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.

Dr. McLeod has reported that he has no relationships relevant to the contents of this paper to disclose. Dr. Gersh is a member of a Data Safety Monitoring Board for Mount Sinai St. Lukes, Boston Scientific Corporation, Teva Pharmaceutical Industries, St. Jude Medical Inc., Janssen Research & Development, Baxter Healthcare Corporation, Cardiovascular Research Foundation, and Thrombosis Research Institute; and he is a consultant for Janssen Scientific Affairs, Xenon Pharmaceuticals, Cipla Limited, and Armetheon Inc.